Obesity resulting from supernutrition is now the most important factor causing such severe lifestyle-related diseases as diabetes, hypertension and arteriosclerosis. In considering the future life sciences and health sciences, the elucidation of the molecular mechanisms of obesity may be said to be an essential task. It is adipocytes that are directly involved in obesity, and the elucidation of the process of adipocyte generation, if given, will have a direct bearing on the treatment of obesity. With the recent advances in molecular biology, the mechanisms of adipocyte differentiation are being elucidated. It is known that there are a group of key genes and that these form an ingenious information-exchanging network.
The adipocyte differentiation process comprises a complicated series of steps, and adipoblasts differentiate into preadipocytes, which then differentiate into adipocytes. Transcription factors closely related to adipocyte differentiation have recently been discovered in systems using cultured cells or genetically modified individuals, for instance.
PPARs (peroxisome proliferator-activated receptors), the C/EBP (CCAAT/enhancer-binding protein) family and SREBP-1/ADD1 (sterol regulatory element binding protein 1 or adipocyte determination and differentiation-dependent factor 1) are said to be most important transcription factors in adipocyte differentiation.
It has been made clear that PPARs form a family, in which PPARγ is especially important for adipocyte differentiation. Thus, it has been made clear that ectopic expression of PPARγ results in differentiation of adipoblasts and preadipocytes into adipocytes. This result may be said to be evidential of the fact that PPARγ plays an important roll in adipocyte differentiation.
Like PPARs, C/EBPs form a family and, recently, it has been found that C/EBPα, like PPARγ, functions as a master regulator in adipocyte differentiation. Further, C/EBPβ and C/EBPδ are considered to be expressed in the early stage of differentiation, controlling the expression of C/EBPα and PPARγ.
While SREBP1/ADD1 is known to promote the differentiation of adipocytes, it has also been demonstrated that it is involved in PPARγ ligand formation in the process of adipocyte differentiation.
It has been demonstrated that the above-mentioned three transcription factor groups (PPAR, C/EBP, SREBP1/ADD1) make crosstalks, whereby the differentiation process goes on.
It has been demonstrated that the expression of the above three transcription factor groups increases from the relatively early stage of adipocyte differentiation. They are regarded as master regulators controlling the expression of a plurality of target genes. It is known that when these transcription factors are considered from the expression stage viewpoint, the expression of C/EBPβ and C/EBPδ increases in the relatively early stage. However, what gene or genes are activated in the earliest stage of differentiation of preadipocytes into adipocytes, namely within a half day (12 hours) from the start of differentiation, has been little clarified.
Analyses and/or specification as to whether the genes activated in the earliest stage of differentiation of preadipocytes into adipocytes, namely within 12 hours from the start of differentiation, are expressed or not, the levels thereof, the occurrence or nonoccurrence of proteins as gene products, the amounts thereof and the sites of expression thereof, if the genes are expressed, as well as gene mutation analysis may serve to provide factors very important in elucidating the mechanisms of obesity, further understanding the progressive state of obesity properly, and making use of the thus-obtained findings in the prevention or treatment of obesity. For that purpose, it is desirable to identify such genes as well as the proteins, which are products of such genes, and detect or assay such genes or proteins.
Accordingly, it is an object of the present invention to find out a gene capable of being activated within 12 hours from the start of differentiation of preadipocytes into adipocytes and provide a vector containing that gene, a transformant harboring that vector, a protein produced from that transformant, an antibody specific to that protein, a method of producing that protein, an agonist or antagonist to that protein, a pharmaceutical composition or diagnostic composition containing one or more of such compounds.